Lipid Oxidation Products Have Opposite Effects on Calcifying Vascular Cell and Bone Cell Differentiation: A Possible Explanation for the Paradox of Arterial Calcification in Osteoporotic Patients
Open accessAbstract
Abstract Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral in vascular walls and its simultaneous loss from bone. To assess the potential role of lipoproteins in both processes, we examined the effects of minimally oxidized low-density lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formation of extensive areas of calcification. Similar to MM-LDL, oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (ox-PAPC) and the isoprostane 8-iso prostaglandin E 2 but not PAPC or isoprostane 8-iso prostaglandin F 2α induced alkaline phosphatase activity and differentiation of CVCs. In contrast, MM-LDL and the above oxidized lipids inhibited differentiation of the MC3T3-E1 bone cells, as evidenced by their stimulatory effect on proliferation and their inhibitory effect on the induction of alkaline phosphatase and calcium uptake. These results suggest that specific oxidized lipids may be the common factors underlying the pathogenesis of both atherosclerotic calcification and osteoporosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In vitro, oxidized low-density lipoprotein and several oxidized phospholipid species promote calcification of isolated vascular cells.
“Work conducted in vitro has shown that Ox-LDL and several oxidized phospholipid (Ox-PL) species promote the calcification of isolated vascular cells45.”
From Calcific aortic stenosis (2016) · cites this paper as [45]
The ‘Effect of MM-LDL on CVC Morphology and Nodules’ section reports larger areas of calcifying condensations in cultured vascular cells treated with minimally oxidized LDL. The ‘Effect of Ox-PAPC and Iso-PGE2 on Alkaline Phosphatase Activity’ section reports that ox-PAPC increased a marker of osteoblastic differentiation, but it does not show calcification promoted by several distinct oxidized phospholipid species. The available passages have no page numbers. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Epstein, F. H., Steinberg, D. I., Parthasarathy, S., Carew, T. E., Khoo, J. C., & Witztum, J. L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198904063201407 · Cited by 6,425 · see citing works
Role of oxidized low density lipoprotein in atherogenesis.
Witztum, J. L., & Steinberg, D. H. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115499 · Cited by 2,682 · see citing works
Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats
Maniatopoulos, C., Sodek, J., & Melcher, A. H. (1988) · Cell and Tissue Research · doi:10.1007/bf00225804 · Cited by 1,322 · see citing works
Watson, A. D., Berliner, J. A., Hama, S. Y., Du, B. N. L., Faull, K. F., Fogelman, A. M., & Navab, M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118359 · Cited by 1,153 · see citing works
Self-citationStein, G. S., & Lian, J. B. (1993) · Endocrine Reviews · doi:10.1210/edrv-14-4-424 · Cited by 1,058 · see citing works
Bone morphogenetic protein expression in human atherosclerotic lesions.
Boström, K. I., Watson, K. E., Horn, S. E. V., Wortham, C., Herman, I. M., & Demer, L. L. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116391 · Cited by 1,020 · see citing works
Self-citationMinimally modified low density lipoprotein stimulates monocyte endothelial interactions.
Berliner, J. A., Territo, M., Sevanian, A., Ramin, S., Kim, J. A., Bamshad, B., Esterson, M., & Fogelman, A. M. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114562 · Cited by 924 · see citing works
Self-citationGiachelli, C. M., Bae, N., de Almeida, M. A. G., Denhardt, D. T., Alpers, C. E., & Schwartz, S. M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116755 · Cited by 641 · see citing works
Osteoblast and chondroblast differentiation
Aubin, J. E., Liu, F., Malaval, L., & Gupta, A. (1995) · Bone · doi:10.1016/8756-3282(95)00183-e · Cited by 596 · see citing works
Molecular Biology of Matrix Vesicles
Anderson, H. C. (1995) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-199505000-00034 · Cited by 585 · see citing works
TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify.
Watson, K. E., Boström, K. I., Ravindranath, R. M. H., Lam, T., Norton, B., & Demer, L. L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117205 · Cited by 460 · see citing works
Self-citationMorrow, J. D., & Roberts, L. J. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)02072-1 · Cited by 443 · see citing works
Stary, H. C. (1990) · European Heart Journal · doi:10.1093/eurheartj/11.suppl_e.3 · Cited by 405 · see citing works
The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis
Hall, B. K., & Miyake, T. (1992) · Anatomy and Embryology · doi:10.1007/bf00174948 · Cited by 377 · see citing works
β-Glycerophosphate Accelerates Calcification in Cultured Bovine Vascular Smooth Muscle Cells
Shioi, A., Nishizawà, Y., Jono, S., Koyama, H., Hosoi, M., & Morii, H. (1995) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.15.11.2003 · Cited by 290 · see citing works
Osteocyte density changes in aging and osteoporosis
Mullender, M. G., van der Meer, D. D., Huiskes, R., & Lips, P. (1996) · Bone · doi:10.1016/8756-3282(95)00444-0 · Cited by 265 · see citing works
Parhami, F., Fang, Z. T., Fogelman, A. M., Andalibi, A., Territo, M., & Berliner, J. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116590 · Cited by 256 · see citing works
Self-citationMatrix Vesicles in Atherosclerotic Calcification
Tanimura, A., McGregor, D. H., & Anderson, H. C. (1983) · Experimental Biology and Medicine · doi:10.3181/00379727-172-41542 · Cited by 219 · see citing works
Minimally modified low density lipoprotein is biologically active in vivo in mice.
Liao, F., Berliner, J. A., Mehrabian, M., Navab, M., Demer, L. L., Lusis, A. J., & Fogelman, A. M. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115261 · Cited by 210 · see citing works
Self-citationKatsuda, S., Okada, Y., Minamoto, T., Oda, Y., Matsui, Y., & Nakanishi, I. (1992) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.12.4.494 · Cited by 205 · see citing works
Coronary arterial calcification as an active process: A new perspective on an old problem
Doherty, T. M., & Detrano, R. (1994) · Calcified Tissue International · doi:10.1007/bf00301683 · Cited by 185 · see citing works
Banks, L. M., Lees, B., MacSweeney, J. E., et al. (1994) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1994.tb02024.x · Cited by 165 · see citing works
A Skeleton in the Atherosclerosis Closet
Demer, L. L. (1995) · Circulation · doi:10.1161/01.cir.92.8.2029 · Cited by 149 · see citing works
Self-citationCalcification of the aorta and osteoporosis. A roentgenographic study
Boukhris, R. (1972) · JAMA · doi:10.1001/jama.219.10.1307 · Cited by 129 · see citing works
Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry
Xu, H., Watkins, B. A., & Seifert, M. F. (1995) · Calcified Tissue International · doi:10.1007/bf00298885 · Cited by 118 · see citing works
Guyton, J. R., & Klemp, K. F. (1993) · PubMed · Cited by 99 · see citing works
Laroche, M., Pouillès, J. M., Ribot, C. A., Bendayan, P., Bernard, J.-C., Boccalon, H., & Mazières, B. (1994) · Clinical Rheumatology · doi:10.1007/bf02243003 · Cited by 90 · see citing works
Colocalization of cholesterol and hydroxyapatite in human atherosclerotic lesions
Hirsch, D., Azoury, R., Sarig, S., et al. (1993) · Calcified Tissue International · doi:10.1007/bf00308315 · Cited by 78 · see citing works
Vukičević, S., Luyten, F. P., & Reddi, A. H. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90873-l · Cited by 78 · see citing works
Noda, M., VOGEL, R. L., HASSON, D. M., et al. (1990) · Endocrinology · doi:10.1210/endo-127-1-185 · Cited by 68 · see citing works
Gopaul, N. K., Nourooz‐Zadeh, J., Mallet, A. I., et al. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00628-8 · Cited by 63 · see citing works
Inhibition of the calcification of porcine valve tissue by selective lipid removal
Jorge‐Herrero, E., Hernando, P. F., de la Tone, N., et al. (1994) · Biomaterials · doi:10.1016/0142-9612(94)90036-1 · Cited by 56 · see citing works
Aortic size and aortic calcification
Mitchell, J. R. A., & ADAMS, J. H. (1977) · Atherosclerosis · doi:10.1016/0021-9150(77)90162-9 · Cited by 53 · see citing works
Characterization of a Gla-containing protein from calcified human atherosclerotic plaques.
Gijsbers, B. L. M. G., van Haarlem, L. J. M., Soute, B. A. M., et al. (1990) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.10.6.991 · Cited by 52 · see citing works
Role of serum in the developmental expression of alkaline phosphatase in MC3T3‐E1 osteoblasts
Yohay, D. A., Zhang, J., Thrailkill, K. M., et al. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041580311 · Cited by 49 · see citing works
Ouchi, Y., Akishita, M., SOUZA, A. C. D., et al. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb38743.x · Cited by 49 · see citing works
Broulik, P. D., & Kapitola, J. (1993) · PubMed · Cited by 46 · see citing works
Embryonic alkaline phosphatase is expressed at M-phase in the spermatogenic lineage of the mouse
Narisawa, S., Hofmann, M.-C. C., Ziomek, C. A., et al. (1992) · Development · doi:10.1242/dev.116.1.159 · Cited by 41 · see citing works
Clinical implications of the molecular biology of the renin-angiotensin system
Soubrier, F., & Corvol, P. L. (1990) · European Heart Journal · doi:10.1093/eurheartj/11.suppl_d.3 · Cited by 37 · see citing works
Untersuchungen �ber arteriosklerotische Ver�nderungen der Knochenarterien
Ramseier, E. (1962) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00957640 · Cited by 32 · see citing works
Inhibition ofin vitro mineralization by aluminum in a clonal osteoblastlike cell line, MC3T3-E1
Ikeda, K., Matsumoto, T., Morita, K., et al. (1986) · Calcified Tissue International · doi:10.1007/bf02555198 · Cited by 29 · see citing works
Studies of the Levamisole inhibitory effect on rat stromal‐cell commitment to mineralization
Klein, B., Gal, I., & Segal, D. (1993) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240530204 · Cited by 27 · see citing works
Prasad, M. R., & Das, D. K. (1989) · Free Radical Research Communications · doi:10.3109/10715768909087965 · Cited by 23 · see citing works
Rossi, M. A., Braile, D. M., Teixeira, M., et al. (1990) · PubMed · Cited by 19 · see citing works
Visscher, D. W., Micale, M. A., & Crissman, J. D. (1993) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240531122 · Cited by 17 · see citing works
Significance of coronary artery calcification.
Baron, M. G. (1994) · Radiology · doi:10.1148/radiology.192.3.8058921 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [8]8. Katsuda S, Okada Y, Minamoto T, Oda Y, Matsui Y, Nakanishi I. Collagens in human atherosclerosis. Arterioscler Thromb. 1992;12: 494-502.
- [9]9. Watson KE, Bostrom K, Ravindranath R, Lam T, Norton B, Demer LL. TGF-/31 and 25-hydroxycholesterol stimulate osteoblast-like cells to calcify. J Clin Invest. 1994;93:2106-2113.
- [17]17. Guyton JR, Klemp KF. Transitional features in human atheroscle- rosis. Am J Pathol. 1993;143:1444-1457.
- [23]23. Liao F, Berliner JA, Mehrabian M, Navab M, Demer LL, Lusis AJ, Fogelman AM. MM-LDL is biologically active in vivo in mice. J Clin Invest. 1991;87:2253-2257.
- [24]24. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. / Clin Invest. 1995;96: 2882-2891.
- [29]29. Boukhris R, Becker KL. Calcification of the aorta and osteoporosis. JAMA. 1972;219:1307-1311.
- [37]37. Ikeda K, Matsumoto T, Morita K, Kurokawa K, Ogatta E. Inhi- bition of in vitro mineralization by aluminum in a clonal osteo- blastlike cell line, MC3T3-E1. Calcif Tissue Int. 1986;39:319-323.
- [39]39. Aubin JE, Liu F, Malaval L, Gupta AK. Osteoblast and chon- droblast differentiation. Bone. 1995;17:77S-83S.
- [42]42. Ramseier E. Arteriosclerotic lesions of the bone arteries. Virchows Arch [A]. 1962;336:77-86.
Cited by
Sorted by citations
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483 · see citing works
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601 · see citing works
Self-citationLindman, B. R., Clavel, M.-A., Mathieu, P., Iung, B., Lancellotti, P., Otto, C. M., & Pibarot, P. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.6 · Cited by 982 · see citing works
Rajamannan, N. M., Evans, F. J., Aikawa, E., Grande-Allen, K. J., Demer, L. L., Heistad, D. D., Simmons, C. A., Masters, K. S., Mathieu, P., O'Brien, K. D., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.006767 · Cited by 842 · see citing works
Self-citationDweck, M. R., Boon, N. A., & Newby, D. E. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.02.093 · Cited by 692 · see citing works
Hsu, Y.-H., Venners, S. A., Terwedow, H. A., Feng, Y., Niu, T., Li, Z., Laird, N., Brain, J. D., Cummings, S. R., Bouxsein, M. L., et al. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.1.146 · Cited by 537 · see citing works
Smith, J. G., Luk, K., Schulz, C.-A., Engert, J. C., Do, R., Hindy, G., Rukh, G., Dufresne, L., Almgren, P., Owens, D. S., et al. (2014) · JAMA · doi:10.1001/jama.2014.13959 · Cited by 238 · see citing works
Liberman, M., Bassi, E., Martinatti, M. K., Lario, F. C., Wosniak, J., Pomerantzeff, P. M. A., & Laurindo, F. R. M. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.156745 · Cited by 225 · see citing works
Mohty, D., Pibarot, P., Després, J.-P., Côté, C., Arsenault, B., Cartier, A., Cosnay, P., Couture, C., & Mathieu, P. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.154989 · Cited by 181 · see citing works
Large animal models of cardiovascular disease
Tsang, H. G., Rashdan, N. A., Whitelaw, C. B. A., Corcoran, B. M., Summers, K. M., & MacRae, V. E. (2016) · Cell Biochemistry and Function · doi:10.1002/cbf.3173 · Cited by 154 · see citing works
Is the anti-inflammatory effect of regular exercise responsible for reduced cardiovascular disease?
Wilund, K. R. (2007) · Clinical Science · doi:10.1042/cs20060368 · Cited by 138 · see citing works
Thanassoulis, G., Massaro, J. M., Cury, R., Manders, E., Benjamin, E. J., Vasan, R. S., Cupple, L. A., Hoffmann, U., O'Donnell, C. J., & Kathiresan, S. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.019 · Cited by 114 · see citing works
- Authors
- Parhami, F., Morrow, A. D., Balucan, J., Leitinger, N., Watson, A. D., Tintut, Y., Berliner, J. A., & Demer, L. L.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 1997-04
- Volume
- 17
- Issue
- 4
- Pages
- 680-687
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2130149021
- Cited by
- 619
- References
- 46
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 16 · 2023: 6 · 2022: 15 · 2021: 10 · 2020: 26 · 2019: 9 · 2018: 15 · 2017: 26 · 2016: 24 · 2015: 24 · 2014: 22 · 2013: 29 · 2012: 29
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lincy Foundation
- National Institutes of Health (5r29hl043379-05)
- National Heart, Lung, and Blood Institute (HL 43379, HL3 0568, P01HL030568)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- lipid oxidation products, atherosclerotic calcification, osteoporosis, preosteoblast differentiation, alkaline phosphatase activity, MC3T3-E1 cells, lipoproteins, vascular calcification, bone mineral loss
- MeSH terms
- Alkaline Phosphatase, Animals, Aorta, Calcinosis, Calcium, Cattle, Cell Differentiation, Cell Division, Cells, Cultured, DNA, Lipoproteins, LDL, Muscle, Smooth, Vascular, Osteoblasts, Osteoporosis, Oxidation-Reduction, Dinoprostone, Isoprostanes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
